Burden of rare coding variants reveals genetic heterogeneity between obese and non-obese asthma patients in the African American population.
Asthma
Comorbidity
Obesity
Rare coding variants
Whole genome sequencing (WGS)
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
06 May 2022
06 May 2022
Historique:
received:
22
12
2021
accepted:
19
04
2022
entrez:
6
5
2022
pubmed:
7
5
2022
medline:
11
5
2022
Statut:
epublish
Résumé
Asthma is a complex condition largely attributed to the interactions among genes and environments as a heterogeneous phenotype. Obesity is significantly associated with asthma development, and genetic studies on obese vs. non-obese asthma are warranted. To investigate asthma in the minority African American (AA) population with or without obesity, we performed a whole genome sequencing (WGS) study on blood-derived DNA of 4289 AA individuals, included 2226 asthma patients (1364 with obesity and 862 without obesity) and 2006 controls without asthma. The burden analysis of functional rare coding variants was performed by comparing asthma vs. controls and by stratified analysis of obese vs. non-obese asthma, respectively. Among the top 66 genes with P < 0.01 in the asthma vs. control analysis, stratified analysis by obesity showed inverse correlation of natural logarithm (LN) of P value between obese and non-obese asthma (r = - 0.757, P = 1.90E-13). Five genes previously reported in a genome-wide association study (GWAS) on asthma, including TSLP, SLC9A4, PSMB8, IGSF5, and IKZF4 were demonstrated association in the asthma vs. control analysis. The associations of IKZF4 and IGSF5 are only associated with obese asthma; and the association of SLC9A4 is only observed in non-obese asthma. In addition, the association of RSPH3 (the gene is related to primary ciliary dyskinesia) is observed in non-obese asthma. These findings highlight genetic heterogeneity between obese and non-obese asthma in patients of AA ancestry.
Sections du résumé
BACKGROUND
BACKGROUND
Asthma is a complex condition largely attributed to the interactions among genes and environments as a heterogeneous phenotype. Obesity is significantly associated with asthma development, and genetic studies on obese vs. non-obese asthma are warranted.
METHODS
METHODS
To investigate asthma in the minority African American (AA) population with or without obesity, we performed a whole genome sequencing (WGS) study on blood-derived DNA of 4289 AA individuals, included 2226 asthma patients (1364 with obesity and 862 without obesity) and 2006 controls without asthma. The burden analysis of functional rare coding variants was performed by comparing asthma vs. controls and by stratified analysis of obese vs. non-obese asthma, respectively.
RESULTS
RESULTS
Among the top 66 genes with P < 0.01 in the asthma vs. control analysis, stratified analysis by obesity showed inverse correlation of natural logarithm (LN) of P value between obese and non-obese asthma (r = - 0.757, P = 1.90E-13). Five genes previously reported in a genome-wide association study (GWAS) on asthma, including TSLP, SLC9A4, PSMB8, IGSF5, and IKZF4 were demonstrated association in the asthma vs. control analysis. The associations of IKZF4 and IGSF5 are only associated with obese asthma; and the association of SLC9A4 is only observed in non-obese asthma. In addition, the association of RSPH3 (the gene is related to primary ciliary dyskinesia) is observed in non-obese asthma.
CONCLUSIONS
CONCLUSIONS
These findings highlight genetic heterogeneity between obese and non-obese asthma in patients of AA ancestry.
Identifiants
pubmed: 35524249
doi: 10.1186/s12931-022-02039-0
pii: 10.1186/s12931-022-02039-0
pmc: PMC9078008
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
116Informations de copyright
© 2022. The Author(s).
Références
Am J Epidemiol. 2021 Jan 4;190(1):85-94
pubmed: 32700739
Nat Commun. 2015 Jan 16;6:5965
pubmed: 25591454
J Biol Chem. 2009 Oct 23;284(43):29437-45
pubmed: 19684019
Mol Cell Biol. 2003 Jun;23(12):4267-82
pubmed: 12773569
Nucleic Acids Res. 2017 Jan 4;45(D1):D840-D845
pubmed: 27899611
Nat Genet. 2011 Jul 31;43(9):893-6
pubmed: 21804548
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Am J Hum Genet. 2015 Jul 2;97(1):153-62
pubmed: 26073779
Int J Epidemiol. 2019 Jun 1;48(3):899-907
pubmed: 31005996
J Allergy Clin Immunol. 2018 Apr;141(4):1169-1179
pubmed: 29627041
Am J Hum Genet. 2018 Oct 4;103(4):522-534
pubmed: 30269813
Nat Commun. 2020 Apr 15;11(1):1776
pubmed: 32296059
Int J Gen Med. 2013 Apr 17;6:253-65
pubmed: 23637549
PLoS Genet. 2011 Feb 10;7(2):e1001300
pubmed: 21347282
PLoS One. 2020 Nov 25;15(11):e0242364
pubmed: 33237978
Nat Med. 2015 Sep;21(9):1018-27
pubmed: 26301688
Mol Cell Endocrinol. 2011 Feb 20;333(2):103-11
pubmed: 21134413
Curr Opin Allergy Clin Immunol. 2014 Oct;14(5):381-9
pubmed: 25153337
Am J Pharmacogenomics. 2002;2(3):155-66
pubmed: 12383022
Immunity. 2013 May 23;38(5):998-1012
pubmed: 23684987